Interferon tau (IFNxcfx84) blocks the development of experimental allergic encephalomyelitis (EAE) in mice without associated toxicity; however, the mechanism of such action has not been fully elucidated (Soos et al., 1995). EAE is a murine model useful for studying the demyelinating disease multiple sclerosis (MS) (Zamvil and Steinman, 1990). Myelin basic protein (MBP) has been shown to be one of the primary central nervous system antigens responsible for induction of autoimmunity in the EAE model. Upon immunization with MBP, mice develop clinically observable tail and limb paralysis due to lymphocyte infiltration into the central nervous system accompanied by acute demyelination (Zamvil and Steinman, 1990).
The type I interferons (IFNs), xcex1 and xcex2, have previously been shown to induce suppressor cells that block in vitro antibody production (Johnson and Blalock, 1980). Further, when type I IFNxcfx84-induced suppressor cells were cultured in vitro, they were shown to produce a soluble factor that mediated immunosuppression. Past studies have suggested that xe2x80x9cclassicxe2x80x9d T suppressor cells bear the CD8 phenotype. In addition, IFNxcfx84-induced suppressor cell function occurs via a mechanism similar to that originally observed for type I IFNxcex1 and xcex2 inhibition of antibody production in vitro.
A suppressor mechanism shared by the type I IFNs is the induction of soluble suppressor factors. The identification of the cytokines responsible for the induction of suppressor cells useful in the treatment of autoimmune diseases is provided by the subject invention. Surprisingly, these cytokines act in a synergistic fashion. Although IL-10 (Vieira et al., 1991; Moore et al., 1990) and TGF-xcex2 (for a review see Massague, 1990) have previously been shown to inhibit events associated with autoimmune disease (Chaouat et al., 1995; Rott et al., 1994; Stevens et al., 1994; Johns et al., 1991; Schluesener and Lider, 1989), it was not known that these cytokines are produced by suppressor cells involved in prevention of EAE, nor was the synergistic action of these cytokines or self-reactive T cells known.
The subject invention concerns novel methods for treating autoimmune-related diseases, such as Multiple Sclerosis (MS). The method of the subject invention comprises administering the cytokines interleukin-10 (IL-10) and transforming growth factor-beta (TGF-xcex2), in combination, to a person afflicted with, or predisposed to, an autoimmune disease. When administered in combination, IL-10 and TGF-xcex2 act as suppressive cytokines in a synergistic manner to inhibit the activation of self-reactive T cells in autoimmune diseases. In a further embodiment of the subject method, IL-10 and TGF-xcex2 can be administered in conjunction with IFNxcfx84.